Photochemical sterilization of blood products is the ultimate goal of this project, in which we are quantitating photochemical destruction of virus in blood and blood products and the effects of the process on the native blood components. Initial studies using an XeCl excimer laser characterized the response of virus and blood components as functions of cumulative fluence and peak irradiance. Single and multiple photon photochemical schemes were investigated. Single photon photochemistry resulted in an efficacious treatment range between 10-20 J/cm2 in which a hardy virus is inactivated and platelets and plasma proteins are minimally affected. Multiple photon effects at higher irradiance led to increased protein damage in blood components without increasing efficacy of viral inactivation. Augmentation of this therapeutic window by photochemistry using exogenous agents such as riboflavin, tetracycline, and hemocyanin was investigated with a focus on the adverse effects on platelets and the relative susceptibility of different viruses dependent on the complexity of their coat. The inhibitory effect of serum and albumin on photochemistry was also examined. Proposed work will examine exogenous agents which show strong affinity for binding to DNA and thereby might increase therapeutic efficacy. The high sensitivity of blood platelets to activation and/or damage by photochemical products (e.g., singlet oxygen) has led to a renewed emphasis on optical and immunological methods of monitoring minimal lesions associated with viral inactivation photochemistry as well as standard blood banking techniques of preparation and storage.